tbuckley/cabot-search huggingface dataset:
Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies
Authors: Weng M. Ng, Sofiya Fedosyuk, Solomon English, Gilles Augusto, Adam Berg, Luke Thorley, Anna-Sophie Haselon, Rameswara R. Segireddy, Thomas A. Bowden, Alexander D. Douglas
Journal: Cell Host & Microbe (2022)

Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-G's pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies that can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-Å structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1, that recognize distinct epitopes. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. Targeted mutations can similarly stabilize RABV-G in the pre-fusion conformation, a key step toward structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and this will facilitate the development of improved vaccines and prophylactic antibodies.
Glycan targeting nanoparticle for photodynamic immunotherapy of melanoma
Authors: Yonghyun Choi, Wooic Son, Youngpin Han, Jayoung Chae, Chul-Su Yang, Jonghoon Choi
Journal: Acta Pharmaceutica Sinica B (2022)

Interaction between tumour cells and macrophages enables cancer cells to evade immune detection and clearance by interfering with macrophage phagocytosis. The anti-phagocytic signals regulated by anti-phagocytic proteins are termed "don't eat me" signals; these signals include sialic acid-binding immunoglobulin-type lectin-10 (Siglec-10) and the recently revealed CD24 immune checkpoint (ICP). In this study, we demonstrate that targeting a specific glycan on CD24 exhibits the potential to inhibit ICP. Sambucus nigra agglutinin (SNA), a sialic acid-binding lectin, was employed to block CD24 and to enhance phagocytosis in melanoma tumours. In addition, we prepared SNA-conjugated hollow gold-iron oxide nanoparticles for photothermal therapy of tumours. Our findings show that the combination treatment of SNA-conjugated photothermal nanoparticles and near-infrared exposure successfully augments tumour cell phagocytosis both in vitro and in vivo models.
Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial
Authors: Stephen J. Nicholls, Marc Ditmarsch, John J. Kastelein, Scott P. Rigby, Douglas Kling, Danielle L. Curcio, Nicholas John Alp, Michael H. Davidson
Journal: Nature Medicine (2022)
Birth Outcomes, Health, and Health Care Needs of Childbearing Women following Wildfire Disasters: An Integrative, State-of-the-Science Review
Authors: Jo Evans, Amita Bansal, Danielle A.J.M. Schoenaker, Nicolas Cherbuin, Michael J. Peek, Deborah L. Davis
Journal: Environmental Health Perspectives (2022)

Background: The frequency and severity of extreme weather events such as wildfires are expected to increase due to climate change. Childbearing women, that is, women who are pregnant, soon to be pregnant, or have recently given birth, may be particularly vulnerable to the effect of wildfire exposure. Objectives: This review sought to systematically assess what is known about birth outcomes, health, and health care needs of childbearing women during and after exposure to wildfires. Methods: An integrative review methodology was utilized to enable article selection, data extraction, and synthesis across qualitative and quantitative studies. Comprehensive searches of SCOPUS (including MEDLINE and Embase), CINAHL, PubMed, and Google Scholar identified studies for inclusion with no date restriction. Included studies were independently appraised by two reviewers using the Crowe Critical Appraisal Tool. The findings are summarized and illustrated in tables. Results: Database searches identified 480 records. Following title, abstract, and full text screening, sixteen studies published between 2012 and 2022 were identified for this review. Eleven studies considered an association between in utero exposure to wildfire and impacts on birth weight and length of gestation. One study reported increased rates of maternal gestational diabetes mellitus and gestational hypertension following exposure; whereas one study reported differences in the secondary sex ratio. Two studies reported higher incidence of birth defects following in utero exposure to wildfire smoke. Three studies reported increased mental health morbidity, and one study associated a reduction in breastfeeding among women who evacuated from a wildfire disaster. Discussion: Evidence indicates that wildfire exposure may be associated with changes to birth outcomes and increased morbidity for childbearing women and their babies. These effects may be profound and have long-term and wide-ranging public health implications. This research can inform the development of effective clinical and public health strategies to address the needs of childbearing women exposed to wildfire disaster. https://doi.org/10.1289/EHP10544
De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma
Authors: Diana D. Shi, Milan R. Savani, Michael M. Levitt, Adam C. Wang, Jennifer E. Endress, Cylaina E. Bird, Joseph Buehler, Sylwia A. Stopka, Michael S. Regan, Yu-Fen Lin, Vinesh T. Puliyappadamba, Wenhua Gao, Januka Khanal, Laura Evans, Joyce H. Lee, Lei Guo, Yi Xiao, Min Xu, Bofu Huang, Rebecca B. Jennings, Dennis M. Bonal, Misty S. Martin-Sandoval, Tammie Dang, Lauren C. Gattie, Amy B. Cameron, Sungwoo Lee, John M. Asara, Harley I. Kornblum, Tak W. Mak, Ryan E. Looper, Quang-De Nguyen, Sabina Signoretti, Stefan Gradl, Andreas Sutter, Michael Jeffers, Andreas Janzer, Mark A. Lehrman, Lauren G. Zacharias, Thomas P. Mathews, Julie-Aurore Losman, Timothy E. Richardson, Daniel P. Cahill, Ralph J. DeBerardinis, Keith L. Ligon, Lin Xu, Peter Ly, Nathalie Y.R. Agar, Kalil G. Abdullah, Isaac S. Harris, William G. Kaelin, Samuel K. McBrayer
Journal: Cancer Cell (2022)
Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis
Authors: Y. Grace Cao, Sena Bae, Jannely Villarreal, Madelyn Moy, Eunyoung Chun, Monia Michaud, Jessica K. Lang, Jonathan N. Glickman, Lior Lobel, Wendy S. Garrett
Journal: Cell Host & Microbe (2022)
LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept
Authors: Tamer Coskun, Shweta Urva, William C. Roell, Hongchang Qu, Corina Loghin, Julie S. Moyers, Libbey S. O’Farrell, Daniel A. Briere, Kyle W. Sloop, Melissa K. Thomas, Valentina Pirro, David B. Wainscott, Francis S. Willard, Matthew Abernathy, LaRonda Morford, Yu Du, Charles Benson, Ruth E. Gimeno, Axel Haupt, Zvonko Milicevic
Journal: Cell Metabolism (2022)

With an increasing prevalence of obesity, there is a need for new therapies to improve body weight management and metabolic health. Multireceptor agonists in development may provide approaches to fulfill this unmet medical need. LY3437943 is a novel triple agonist peptide at the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). In vitro, LY3437943 shows balanced GCGR and GLP-1R activity but more GIPR activity. In obese mice, administration of LY3437943 decreased body weight and improved glycemic control. Body weight loss was augmented by the addition of GCGR-mediated increases in energy expenditure to GIPR- and GLP-1R-driven calorie intake reduction. In a phase 1 single ascending dose study, LY3437943 showed a safety and tolerability profile similar to other incretins. Its pharmacokinetic profile supported once-weekly dosing, and a reduction in body weight persisted up to day 43 after a single dose. These findings warrant further clinical assessment of LY3437943.
State of the Science: The Relevance of Symptoms in Cardiovascular Disease and Research: A Scientific Statement From the American Heart Association
Authors: Corrine Y. Jurgens, Christopher S. Lee, Dawn M. Aycock, Ruth Masterson Creber, Quin E. Denfeld, Holli A. DeVon, Linda R. Evers, Miyeon Jung, Gianluca Pucciarelli, Megan M. Streur, Marvin A. Konstam
Journal: Circulation (2022)

Symptoms of cardiovascular disease drive health care use and are a major contributor to quality of life. Symptoms are of fundamental significance not only to the diagnosis of cardiovascular disease and appraisal of response to medical therapy but also directly to patients’ daily lives. The primary purpose of this scientific statement is to present the state of the science and relevance of symptoms associated with cardiovascular disease. Symptoms as patient-reported outcomes are reviewed in terms of the genesis, manifestation, and similarities or differences between diagnoses. Specifically, symptoms associated with acute coronary syndrome, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease are reviewed. Secondary aims include (1) describing symptom measurement methods in research and application in clinical practice and (2) describing the importance of cardiovascular disease symptoms in terms of clinical events and other patient-reported outcomes as applicable.
Neuroblastoma: When differentiation goes awry
Authors: Maged Zeineldin, Anand G. Patel, Michael A. Dyer
Journal: Neuron (2022)

Neuroblastoma is a leading cause of cancer-related death in children. Accumulated data suggest that differentiation arrest of the neural-crest-derived sympathoadrenal lineage contributes to neuroblastoma formation. The developmental arrest of these cell types explains many biological features of the disease, including its cellular heterogeneity, mutational spectrum, spontaneous regression, and response to drugs that induce tumor cell differentiation. In this review, we provide evidence that supports the notion that arrested neural-crest-derived progenitor cells give rise to neuroblastoma and discuss how this concept could be exploited for clinical management of the disease.
Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial
Authors: José Carlos Fernández-García, Rocío Barrios-Rodríguez, Maite Asenjo-Plaza, Bruno Ramos-Molina, María Molina-Vega, Antonio Guzmán-Guzmán, Luis Moreno-León, Elena M. Yubero-Serrano, Francisca Rius-Díaz, Sergio Valdés, Miguel Ángel Martínez-González, José Juan Jiménez-Moleón, Francisco J. Tinahones
Journal: Metabolism (2022)

BackgroundMen with obesity tend to be insulin resistant and often have low-normal testosterone concentrations. We conducted a clinical trial aimed to evaluate potential therapeutic strategies for low testosterone in men with obesity.MethodsWe did a 1-year, parallel, randomized, double-blind, placebo-controlled trial, where we evaluated the independent and combined effects of metformin and testosterone in 106 men with obesity, aged 18–50 years, who had low levels of testosterone and no diabetes mellitus. The primary outcome was change in insulin resistance, measured as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index. Secondary outcomes included changes in total and free serum testosterone, body composition, metabolic variables, erectile function, and health-related quality of life (HRQoL).ResultsIn the intention-to-treat analysis, the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin −2.4, 95 % CI −4.1 to −0.8, p = 0.004; testosterone −2.7, 95 % CI −4.3 to −1.1, p = 0.001; combination −3.4, 95 % CI −5.0 to −1.8, p < 0.001). Combination therapy was not superior to testosterone alone in decreasing insulin resistance (−0.7, 95 % CI −2.3 to 0.9, p = 0.383). Only the combination of metformin plus testosterone significantly increased total and free testosterone concentrations, compared to placebo. No significant changes in body composition (except for a higher decrease in fat mass in the metformin and combination group), metabolic variables, erectile function, or HRQoL were found with any treatment.ConclusionsAmong men with obesity and low testosterone concentrations, the combination of metformin plus testosterone, metformin only, and testosterone only, compared to placebo, reduced insulin resistance with no evidence of additive benefit.
Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+ cells elimination in hepatocellular carcinoma
Authors: Jizhou Tan, Ting Liu, Wenzhe Fan, Jialiang Wei, Bowen Zhu, Yafang Liu, Lingwei Liu, Xiaokai Zhang, Songling Chen, Haibiao Lin, Yuanqing Zhang, Jiaping Li
Journal: Acta Pharmaceutica Sinica B (2022)

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1highCD11b+ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8+ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1highCD11b+ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1highCD11b+ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.
MRG15 aggravates non-alcoholic steatohepatitis progression by regulating the mitochondrial proteolytic degradation of TUFM
Authors: Cheng Tian, Xuewen Min, Yongxu Zhao, Yuchen Wang, Xiaoshan Wu, Situn Liu, Wei Dou, Tingting Zhou, Yan Liu, Rongkui Luo, Zhigang Li, Kathy O. Lui, Yu Li, Ben Zhou, Qiurong Ding
Journal: Journal of Hepatology (2022)
Hepatitis B virus pre-genomic RNA and hepatitis B core-related antigen reductions at week 4 predict favourable hepatitis B surface antigen response upon long-term nucleos(t)ide analogue in chronic hepatitis B
Authors: Lung-Yi Mak, Danny Wong, Alison Kuchta, Martina Hilfiker, Aaron Hamilton, Ning Chow, XianHua Mao, Wai Kay Seto, Man-Fung Yuen
Journal: Clinical and Molecular Hepatology (2022)

We investigated the dynamics of serum HBV pre-genomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in patients receiving nucleos(t)ide analogues (NAs) and their predictability for favourable suppression of serum hepatitis B surface antigen (HBsAg).Serum viral biomarkers were measured at baseline, weeks 4, 12, 24, 36, and 48 of treatment. Patients were followed up thereafter and serum HBsAg level was measured at end of follow-up (EOFU). Favourable HBsAg response (FHR) was defined as ≤100 IU/mL or HBsAg seroclearance upon EOFU.Twenty-eight hepatitis B e antigen (HBeAg)-positive and 36 HBeAg-negative patients (median, 38.2 years old; 71.9% male) were recruited with median follow-up duration of 17.1 years (interquartile range, 12.8-18.2). For the entire cohort, 22/64 (34.4%) achieved FHR. For HBeAg-positive patients, serum HBV pgRNA decline at week 4 was significantly greater for patients with FHR compared to non-FHR (5.49 vs. 4.32 log copies/mL, respectively; P=0.016). The area under the receiver-operating-characteristic curve (AUROC) for week 4 HBV pgRNA reduction to predict FHR in HBeAg-positive patients was 0.825 (95% confidence interval [CI], 0.661-0.989). For HBeAg-negative patients, instead of increase in serum HBcrAg in non-FHR patients, FHR patients had median reduction in HBcrAg at week 4 (increment of 1.75 vs. reduction of 2.98 log U/mL; P=0.023). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.789 (95% CI, 0.596-0.982).Early on-treatment changes of serum HBV pgRNA and HBcrAg at 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in NA-treated CHB patients upon long-term FU.
Repurposing drugs to target nonalcoholic steatohepatitis: Auranofin, a gold-organic molecule complex for the treatment of a specifc complex trait
Authors: Carlos J. Pirola, Silvia Sookoian
Journal: Clinical and Molecular Hepatology (2022)

See the Original "Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF- ÎºB signaling pathways" on page 827.
Safety Monitoring of Pfizer-BioNTech COVID-19 Vaccine Booster Doses Among Children Aged 5–11 Years — United States, May 17–July 31, 2022
Authors: Anne M. Hause, James Baggs, Paige Marquez, Tanya R. Myers, John R. Su, Brandon Hugueley, Deborah Thompson, Julianne Gee, Tom T. Shimabukuro, David K. Shay
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

On May 17, 2022, the Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine to authorize a homologous* booster dose for children aged 5-11 years ≥5 months after receipt of the second primary series dose† (1) based on findings from a clinical trial conducted among 401 children aged 5-11 years (2). To further characterize the safety of booster vaccination in this age group, CDC reviewed adverse events and health impact assessments after receipt of a Pfizer-BioNTech third dose reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events occurring after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system comanaged by CDC and FDA. During May 17-July 31, 2022, approximately 657,302 U.S. children aged 5-11 years received a third Pfizer-BioNTech dose (either a third primary series dose administered to immunocompromised children or a booster dose administered to immunocompetent children)§; 3,249 Pfizer-BioNTech third doses were reported to v-safe for children in this age group. Local and systemic reactions were reported to v-safe after a second dose and a third dose with similar frequency; some reactions (e.g., pain) were reported to be moderate or severe more frequently after a third dose. VAERS received 581 reports of adverse events after receipt of a Pfizer-BioNTech third dose by children aged 5-11 years; 578 (99.5%) reports were considered nonserious, and the most common events reported were vaccine administration errors. Three (0.5%) reports were considered serious; no reports of myocarditis or death were received. Local and systemic reactions were common among children after Pfizer-BioNTech third dose vaccination, but reports of serious adverse events were rare. Initial safety findings are consistent with those of the clinical trial (2).
Caution Regarding Assessment of Toxic Effects and Survival in Treatment De-escalation With Radiotherapy vs Transoral Surgery for Human Papillomavirus–Associated Oropharyngeal Cancer
Authors: Michael C. Topf, F. Christopher Holsinger, Mihir Patel
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Error in Figure 2
Authors: Bishal Gyawali, Elizabeth Eisenhauer, Michael Brundage
Journal: JAMA Oncology (2022)

Lars Björnebo, MD, MSc; Tobias Nordström, MD, PhD; Andrea Discacciati, PhD; Thorgerdur Palsdottir, PhD; Markus Aly, MD, PhD; Henrik Grönberg, MD, PhD; Martin Eklund, PhD; Anna Lantz, MD, PhD
Participation of Lower and Upper Middle–Income Countries in Oncology Clinical Trials Led by High-Income Countries
Authors: Fidel Rubagumya, Wilma M. Hopman, Bishal Gyawali, Deborah Mukherji, Nazik Hammad, C. S. Pramesh, Mykola Zubaryev, Alexandru Eniu, Audrey T. Tsunoda, Tezer Kutluk, Ajay Aggarwal, Richard Sullivan, Christopher M. Booth
Journal: JAMA Network Open (2022)

Many randomized clinical trials (RCTs) led by high-income countries (HICs) now enroll patients from lower middle-income countries (LMICs) and upper middle-income countries (UMICs). Although enrolling diverse populations promotes research collaborations, there are issues regarding which countries participate in RCTs and how this participation may contribute to global research.
Ptchd1 mediates opioid tolerance via cholesterol-dependent effects on μ-opioid receptor trafficking
Authors: Nycole Maza, Dandan Wang, Cody Kowalski, Hannah M. Stoveken, Maria Dao, Omar K. Sial, Andrew C. Giles, Brock Grill, Kirill A. Martemyanov
Journal: Nature Neuroscience (2022)
Precision Medicine and Sickle Cell Disease
Authors: Sara El Hoss, Wassim El Nemer, David C. Rees
Journal: HemaSphere (2022)

Sickle cell disease (SCD) is characterized by variable clinical outcomes, with some patients suffering life-threatening complications during childhood, and others living relatively symptom-free into old age. Because of this variability, there is an important potential role for precision medicine, in which particular different treatments are selected for different groups of patients. However, the application of precision medicine in SCD is limited by difficulties in identifying different prognostic groups and the small number of available treatments. The main genetic determinant of outcomes in SCD is the underlying β-globin genotype, with sickle cell anemia (HbSS) and hemoglobin SC disease (HbSC) forming the 2 major forms of the disease in most populations of African origin. Although there are clear differences in clinical outcomes between these conditions, treatments approaches are very similar, with little evidence on how to treat HbSC in particular. Other genomic information, such as the co-inheritance of α-thalassemia, or high fetal hemoglobin (HbF) levels, is of some prognostic value but insufficient to determine treatments. Precision medicine is further limited by the fact that the 2 main drugs used in SCD, penicillin and hydroxyurea, are currently recommended for all patients. Newer treatments, such as crizanlizumab and voxelotor, raise the possibility that groups will emerge who respond best to particular drugs or combinations. Perhaps the best current example of precision medicine in SCD is the selective use of blood transfusions as primary stroke prevention in children with evidence of cerebral vasculopathy. More precise treatments may emerge as we understand more about the pathology of SCD, including problems with erythropoiesis.